Multinucleation in vivo occurs as a physiological process, e.g. multinucleated giant cells in inflammation. Another nice example is (rodent) liver. There is a clear pattern for the occurrence (and disappearance ) of bi-nuclear hepatocytes during growth (newborn, juvenile, adult) or regeneration. I think the best description (although an old one!) is by James J, 1977 Eur J Cell Biol 15:410-419 and James J et al Eur J Cell Biol 19:222-226. A somewhat more recent one with pretty much the same findings is by Melchiorri C et al 1993 Carcinogenesis, 14 1825-1830.

Under the influence of chemical carcinogens, bi-nucleated hepatocytes decrease in number in the liver of rats and stay decreased for a long time after the end of exposure to the carcinogen (Enzmann et al. 1995, Carcinogenesis, 16, 1351-1355).

Multinucleation in vitro (probably the result of cell fusion) seems to have little meaning for in vivo processes, see also Babak Nami’s question: What is this kind of morphology.

Therefore, I would be hesitant to consider multinucleation a strong indicator of genomic instability.

An abnormal number of centrosomes: yes, that should result in problems / damage during mitoses. In histology, tripolar mitoses have been regarded as characteristic for malignancy.

Bottom line: an unphysiological number of centrosomes seems to be more indicative for genomic istability than mere multinucleation.

Thanks for the response Harald. I am particularly interested in age-related (primary cells in culture) and HPV E6 induced multinucleation/rereplication. We show that at least a portion of the bi and multinucleated cells are formed when cells undergo one or two rounds of re-replication, respectively. We are, as a result, differentiating between bi-nucleation (2 nuclei, one round of re-replication) and multi-nucleation (3+ nuclei, and likely more than 1 round of multinucleation). Supporting our idea that multincleated cells represent re-replication events, we have been able to show by FACS analysis that HPV E6 expression results in an increased population of cells with >4N DNA content.

We did observe some rare examples of tripolar mitoses and chromosome missegregation, but we were not specifically looking for this. As a result the number of events we observed are to low to make any claims or conclusions in that regards.

Still if I interpret your answer correctly, it sounds like you would feel more than comfortable describing these events are evidence for genomic instability.